Objective: Investigation of possible etiological relationships between proteolytic enzyme activities and the onset of irreversible shock. Identification of enzymes released and determination of specific effects of such enzymes with respect to possible roles in the development of irreversibility. Background: Physiological changes developing during shock which result in irreversibility have been long accepted as specific phenomena. Neither the exact nature of such phenomena nor the etiological factors responsible for their development have been well defined. The concept of the "target organ" and its responsibility for irreversibility gained considerable popularity because of consistent changes seen in canine preparations (1-3). The liver, pancreas, small intestine, and occasionally the lung have been organs primarily implicated (1-16). Subhuman primate studies have resulted in marked differences from those observations seen in the dog (17-20). Observed species in hemodynamics (18, 20, 21), length of survival (22-24), coagulation changes (25), and metabolic alterations (26-28, 17) have led to the obvious conclusion that canine observations need re-evaluation. Although not necessarily negating work done in the dog, these observations create the necessity of delineating those areas of significant species differences so that clinical applicability of observations in the laboratory may be more specific. Lysosomal- orproteolytic-enzymes have received significant attention relative to an etiological role in irreversibility. Recent work in our laboratory (29), in addition to cellular metabolism studies (30,31), has suggested that elevation of circulating hydrolases may represent a reflection of cellular death and have a relatively small etiological role in the development of irreversibility. Evaluation of the potential effect of such enzymes, especially as related to their role during shock, is essential. The multiplicity of such enzymes and their sources and the potential for contribution toward changes in such related factors as vasoactive peptides creates unthinkable complexity in attempts for identification. The studies outlined in the protocol explore the possibility of proteolysis secondary to release of lysosomal enzymes. This is done without the necessity of previous specific identification of such enzymes. Later identification and administration to isolated ex vivo organs (Text Truncated - Exceeds Capacity)